Sunday, April 12, 2015

TNF-α sensing by brain is required for early mobilization of adaptive immune system

Very few studies have been done with the focus on understanding the relationship between brain and adaptive immune system. In principle, rapid sensing of peripheral insults by neurons and information analysis by brain could facilitate efficient recruitment of adaptive immune cells.

Initially, the authors showed that direct injection of 10pg of TNF-α into mouse hypothalamus induced rapid mobilization of T and B cells in the spleen and adipose tissue (similar effect was seen with an intravenous L.M infection).

Next, the authors showed that such mobilization of adaptive immune cells during an intravenous L.M infection was reduced when TNF-α antagonist was injected into hypothalamus.

Similarly, such mobilization of adaptive immune cells in the spleen and adipose tissueduring an intravenous L.M infection was reduced when TNF-α signaling was inhibited in hypothalamus by shRNA.

Conversely, when TNF-R deficient mice were injected in the hypothalamus with lentivirus construct encoding TNFR1, mobilization of adaptive immune cells in the spleen and adipose tissuewas restoredduring an intravenous L.M infection.

Furthermore, sympathetic denervation of adipose tissue also abolished mobilization of adaptive immune cells in the spleen and adipose tissue in response to hypothalamic TNF-α injection.

Next, the authors showed that mobilization of adaptive immune cells in the spleen and adipose tissue in response to an intravenous L.M infection or hypothalamic TNF-α injection was reversed by lypolysis inhibitor, implying that brain signaled the adaptive immune system via lipid metabolites.

In summary, these results points to a novel inter-talk mechanism, based on lypolysis products, between brain and adaptive immune system at an early stage of infection. Right now it is not clear whether this brain-assisted rapid mobilization of adaptive immune cells could translate into efficient immune response against infection later on.